Epigenetic mechanisms of age-dependent KIR2DL4 expression in T cells

Guangjin Li, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Killer Ig-like receptor (KIR) expression is mostly restricted to NK cells controlling their activation. With increasing age, KIRs are expressed on T cells and contribute to age-related diseases. We examined epigenetic mechanisms that determine the competency of T cells to transcribe KIR2DL4. Compared with Jurkat cells and CD4+CD28+ T cells from young individuals, DNA methyltransferase (DNMT) inhibition was strikingly more effective in T cells from elderly adults and the CD4+CD28- T cell line HUT78 to induce KIR2DL4 transcription. In these susceptible cells, the KIR2DL4 promoter was partially demethylated, and dimethylated H3-Lys 4 was increased, and all other histone modifications were characteristic for an inactive promoter. In comparison, NK cells had a fully demethylated KIR2DL4 promoter and the full spectrum of histone modifications indicative of active transcription with H3 and H4 acetylation, di- and trimethylated H3-Lys 4, and reduced, dimethylated H3-Lys 9. These results suggest that an increased competency of T cells to express KIR2DL4 with aging is conferred by a selective increase in H3-Lys 4 dimethylation and limited DNA demethylation. The partially accessible promoter is sensitive to DNMT inhibition, which is sufficient to induce full transcription without further histone acetylation and methylation.

Original languageEnglish (US)
Pages (from-to)824-834
Number of pages11
JournalJournal of Leukocyte Biology
Volume84
Issue number3
DOIs
StatePublished - Sep 1 2008

Keywords

  • Cellular immunology
  • Cellular senescence
  • Deacetylase
  • Gene expression
  • Molecular biology of aging

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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